This project will address, at scale, improvement of safe use practices for antipsychotic (AP) treatment of Medicaid children. Safe and judicious management of APs poses significant challenges, given hazards that include elevated risk of Type 2 diabetes, weight gain, hyperglycemia, hyperlipidemia, and potential long-term impact on brain development. Safety evidence and guidelines highlight the importance of several key safe-use practices that can help mitigate these risks, including monitoring blood glucose and lipids; avoiding concurrent use of multiple different APs; first-line use of non-pharmacological mental health services; and minimizing use among pre-school children. Prior AHRQ-supported projects have led to HEDIS/CMS quality metrics for these practices, but their implementation is highly inconsistent. Many state initiatives have been implemented to improve these safe-use practices, but the impact of alternative strategies for increasing safe-use is unknown. Evidence on their effects is critically needed. We will use a mixed-methods strategy to identify and document state implementation of safe-use initiatives; assess their impact on safe use metrics; investigate causal mechanisms underlying effectiveness; and actively disseminate results to state decisionmakers, health plans, clinical communities, and other stakeholders. This process will support translation, implementation, and improvement of effective strategies across states. We will provide a comprehensive analysis of systems-level strategies, using a national survey and case studies in 8 purposively sampled states, to investigate distinctive approaches. We will use key informant interviews and systematic document review to identify implementation timelines, strategies, causal mechanisms, barriers and solutions, and tools utilized. We will then use Medicaid claims data to assess change in the use of the targeted practices following the implementation of state systems-level strategies, using difference-in-difference, triple-difference and other modeling strategies. States that did not implement similar initiatives will serve as comparators. Finally, we will actively disseminate an evidence-informed toolkit to state and stakeholder communities, utilizing active dissemination strategies successfully employed in prior AHRQ-supported partnerships. This toolkit will be developed to facilitate a self- assessment and prioritization of improvement initiatives, identification of other state strategies, and provide quality improvement and evaluation tools to assess effectiveness over time. Evidence development and active dissemination will assure that evidence on effective system-improvement processes is available, understood, and effectively used to improve patient safety across populations of vulnerable children served by state Medicaid/CHIP systems and reduce AP-related harms.